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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Alteration of fatty-acid-metabolizing enzymes affects mitochondrial form and function in hereditary spastic paraplegia
American Journal of Human Genetics, Volume 91, No. 6, Year 2012
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Description
Hereditary spastic paraplegia (HSP) is considered one of the most heterogeneous groups of neurological disorders, both clinically and genetically. The disease comprises pure and complex forms that clinically include slowly progressive lower-limb spasticity resulting from degeneration of the corticospinal tract. At least 48 loci accounting for these diseases have been mapped to date, and mutations have been identified in 22 genes, most of which play a role in intracellular trafficking. Here, we identified mutations in two functionally related genes (DDHD1 and CYP2U1) in individuals with autosomal-recessive forms of HSP by using either the classical positional cloning or a combination of whole-genome linkage mapping and next-generation sequencing. Interestingly, three subjects with CYP2U1 mutations presented with a thin corpus callosum, white-matter abnormalities, and/or calcification of the basal ganglia. These genes code for two enzymes involved in fatty-acid metabolism, and we have demonstrated in human cells that the HSP pathophysiology includes alteration of mitochondrial architecture and bioenergetics with increased oxidative stress. Our combined results focus attention on lipid metabolism as a critical HSP pathway with a deleterious impact on mitochondrial bioenergetic function. © 2012 The American Society of Human Genetics.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3516610/bin/mmc1.pdf
Authors & Co-Authors
Tesson, Christelle
France, Paris
Inserm
France, Paris
Institut du Cerveau et de la Moelle Épinière
France, Paris
Cnrs Centre National de la Recherche Scientifique
France, Paris
École Pratique Des Hautes Études
Nawara, Magdalena
France, Paris
Inserm
France, Paris
Institut du Cerveau et de la Moelle Épinière
France, Paris
Cnrs Centre National de la Recherche Scientifique
Salih, Mustafa Abdalla M.
Saudi Arabia, Riyadh
College of Medicine
Rossignol, Rodrigue
France, Bordeaux
Maladies Rares : Génétique et Métabolisme Mrgm
Zaki, Maha S.
Egypt, Giza
National Research Centre
Al-Balwi, Mohammed Ali
Saudi Arabia, Riyadh
King Abdulaziz Medical City - Riyadh
Saudi Arabia, Riyadh
King Saud Bin Abdulaziz University for Health Sciences
Schüle, Rebecca
Germany, Tubingen
Hertie-institut Für Klinische Hirnforschung
Mignot, Cyril
France, Paris
Ap-hp Assistance Publique - Hopitaux de Paris
Obre, Émilie
France, Bordeaux
Maladies Rares : Génétique et Métabolisme Mrgm
Bouhouche, Ahmed
Morocco, Rabat
Faculté de Médecine et de Pharmacie de Rabat
Santorelli, Filippo Maria
Italy, Calambrone
Istituto Di Ricovero e Cura a Carattere Scientifico Fondazione Stella Maris
Durand, Christelle Marie
France, Bordeaux
Maladies Rares : Génétique et Métabolisme Mrgm
Oteyza, Andrés Caballero
Germany, Tubingen
Hertie-institut Für Klinische Hirnforschung
El-Hachimi, Khalid Hamid
France, Paris
Inserm
France, Paris
Institut du Cerveau et de la Moelle Épinière
France, Paris
Cnrs Centre National de la Recherche Scientifique
France, Paris
École Pratique Des Hautes Études
Al-Drees, Abdul Majeed
Saudi Arabia, Riyadh
College of Medicine
Bouslam, Naïma
Morocco, Rabat
Faculté de Médecine et de Pharmacie de Rabat
Lamari, Foudil
France, Paris
Ap-hp Assistance Publique - Hopitaux de Paris
Elmalik, Salah A.
Saudi Arabia, Riyadh
College of Medicine
Kabiraj, Mohammad Muslim Uddin
Saudi Arabia, Riyadh
Riyadh Military Hospital
Seidahmed, Mohammed Zain
Saudi Arabia, Riyadh
Security Forces Hospital Program Riyadh
Esteves, Typhaine
France, Paris
Inserm
France, Paris
Institut du Cerveau et de la Moelle Épinière
France, Paris
Cnrs Centre National de la Recherche Scientifique
Gaussen, Marion
France, Paris
Inserm
France, Paris
Institut du Cerveau et de la Moelle Épinière
France, Paris
Cnrs Centre National de la Recherche Scientifique
Monin, Marie Lorraine
France, Paris
Inserm
France, Paris
Institut du Cerveau et de la Moelle Épinière
France, Paris
Cnrs Centre National de la Recherche Scientifique
Gyapay, Gábor
France, Evry
Genoscope - Centre National de Séquençage
Lechner, Doris
France, Evry
Centre National de Recherche en Génomique Humaine
González, Michael Anthony
United States, Miami
University of Miami Leonard M. Miller School of Medicine
Depienne, Christel
France, Paris
Inserm
France, Paris
Institut du Cerveau et de la Moelle Épinière
France, Paris
Cnrs Centre National de la Recherche Scientifique
France, Paris
Ap-hp Assistance Publique - Hopitaux de Paris
Mochel, Fanny
France, Paris
Inserm
France, Paris
Institut du Cerveau et de la Moelle Épinière
France, Paris
Cnrs Centre National de la Recherche Scientifique
France, Paris
Ap-hp Assistance Publique - Hopitaux de Paris
Lavie, Julie
France, Bordeaux
Maladies Rares : Génétique et Métabolisme Mrgm
Schöls, Ludger
Germany, Tubingen
Hertie-institut Für Klinische Hirnforschung
Germany, Bonn
Deutsches Zentrum Für Neurodegenerative Erkrankungen
Lacombe, Didier
France, Bordeaux
Maladies Rares : Génétique et Métabolisme Mrgm
France, Talence
Centre Hospitalier Universitaire de Bordeaux
Yahyaoui, Mohamed
Morocco, Rabat
Faculté de Médecine et de Pharmacie de Rabat
Al-Abdulkareem, Ibrahim
Saudi Arabia, Riyadh
King Saud Bin Abdulaziz University for Health Sciences
Züchner, Stephan L.
United States, Miami
University of Miami Leonard M. Miller School of Medicine
Yamashita, Atsushi
Japan, Tokyo
Teikyo University
Benomar, Ali
Morocco, Rabat
Faculté de Médecine et de Pharmacie de Rabat
Goizet, Cyril
France, Bordeaux
Maladies Rares : Génétique et Métabolisme Mrgm
France, Talence
Centre Hospitalier Universitaire de Bordeaux
Dürr, Alexandra
France, Paris
Inserm
France, Paris
Institut du Cerveau et de la Moelle Épinière
France, Paris
Cnrs Centre National de la Recherche Scientifique
France, Paris
Ap-hp Assistance Publique - Hopitaux de Paris
Gleeson, Joseph G.
United States, La Jolla
Department of Neurosciences
Darios, Frédéric D.
France, Paris
Inserm
France, Paris
Institut du Cerveau et de la Moelle Épinière
France, Paris
Cnrs Centre National de la Recherche Scientifique
Brice, Alexis
France, Paris
Inserm
France, Paris
Institut du Cerveau et de la Moelle Épinière
France, Paris
Cnrs Centre National de la Recherche Scientifique
France, Paris
Ap-hp Assistance Publique - Hopitaux de Paris
Stévanin, Giovanni
France, Paris
Inserm
France, Paris
Institut du Cerveau et de la Moelle Épinière
France, Paris
Cnrs Centre National de la Recherche Scientifique
France, Paris
École Pratique Des Hautes Études
France, Paris
Ap-hp Assistance Publique - Hopitaux de Paris
Statistics
Citations: 177
Authors: 42
Affiliations: 22
Identifiers
Doi:
10.1016/j.ajhg.2012.11.001
ISSN:
00029297
e-ISSN:
15376605
Research Areas
Genetics And Genomics